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Divergent effects of glutathione depletion on isocitrate dehydrogenase 1 and the pentose phosphate pathway in hamster liver
The liver regenerates NADPH via multiple pathways to maintain redox balance and reductive biosynthesis. The pentose phosphate pathway (PPP) contributes to hepatic lipogenesis by supplying NADPH, and it is thought to play a major role in response to oxidative stress. This study determined the signifi...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435027/ https://www.ncbi.nlm.nih.gov/pubmed/32812387 http://dx.doi.org/10.14814/phy2.14554 |
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author | Jin, Eunsook S. Lee, Min H. Malloy, Craig R. |
author_facet | Jin, Eunsook S. Lee, Min H. Malloy, Craig R. |
author_sort | Jin, Eunsook S. |
collection | PubMed |
description | The liver regenerates NADPH via multiple pathways to maintain redox balance and reductive biosynthesis. The pentose phosphate pathway (PPP) contributes to hepatic lipogenesis by supplying NADPH, and it is thought to play a major role in response to oxidative stress. This study determined the significance of the PPP and related NADPH‐regenerating enzymes in the liver under oxidative stress. Fasted hamsters received acetaminophen (400 mg/kg) to deplete glutathione in the liver and [U‐(13)C(3)]glycerol to measure the PPP activity by analysis of (13)C distribution in plasma glucose. Blood and liver were harvested to assess NADPH‐producing enzymes, antioxidant defense, PPP, and other relevant biochemical processes. Acetaminophen caused glutathione depletion and decreased activities of glutathione peroxidase and catalase in the liver, but it did not change triglyceride synthesis. Although the PPP is potentially an abundant source of NADPH, its activity was decreased and the expression of glucose 6‐phosphate dehydrogenase remained unchanged after acetaminophen treatment. The effects of acetaminophen on other NADPH‐producing enzymes were complex. Isocitrate dehydrogenase 1 was overexpressed, both isocitrate dehydrogenase 2 and malic enzyme 1 were underexpressed, and methylenetetrahydrofolate dehydrogenase 1 remained unchanged. In summary, isocitrate dehydrogenase 1 was most sensitive to glutathione depletion caused by acetaminophen, but glucose 6‐phosphate dehydrogenase, the regulatory enzyme of PPP, was not. |
format | Online Article Text |
id | pubmed-7435027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74350272020-08-20 Divergent effects of glutathione depletion on isocitrate dehydrogenase 1 and the pentose phosphate pathway in hamster liver Jin, Eunsook S. Lee, Min H. Malloy, Craig R. Physiol Rep Original Research The liver regenerates NADPH via multiple pathways to maintain redox balance and reductive biosynthesis. The pentose phosphate pathway (PPP) contributes to hepatic lipogenesis by supplying NADPH, and it is thought to play a major role in response to oxidative stress. This study determined the significance of the PPP and related NADPH‐regenerating enzymes in the liver under oxidative stress. Fasted hamsters received acetaminophen (400 mg/kg) to deplete glutathione in the liver and [U‐(13)C(3)]glycerol to measure the PPP activity by analysis of (13)C distribution in plasma glucose. Blood and liver were harvested to assess NADPH‐producing enzymes, antioxidant defense, PPP, and other relevant biochemical processes. Acetaminophen caused glutathione depletion and decreased activities of glutathione peroxidase and catalase in the liver, but it did not change triglyceride synthesis. Although the PPP is potentially an abundant source of NADPH, its activity was decreased and the expression of glucose 6‐phosphate dehydrogenase remained unchanged after acetaminophen treatment. The effects of acetaminophen on other NADPH‐producing enzymes were complex. Isocitrate dehydrogenase 1 was overexpressed, both isocitrate dehydrogenase 2 and malic enzyme 1 were underexpressed, and methylenetetrahydrofolate dehydrogenase 1 remained unchanged. In summary, isocitrate dehydrogenase 1 was most sensitive to glutathione depletion caused by acetaminophen, but glucose 6‐phosphate dehydrogenase, the regulatory enzyme of PPP, was not. John Wiley and Sons Inc. 2020-08-18 /pmc/articles/PMC7435027/ /pubmed/32812387 http://dx.doi.org/10.14814/phy2.14554 Text en © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Jin, Eunsook S. Lee, Min H. Malloy, Craig R. Divergent effects of glutathione depletion on isocitrate dehydrogenase 1 and the pentose phosphate pathway in hamster liver |
title | Divergent effects of glutathione depletion on isocitrate dehydrogenase 1 and the pentose phosphate pathway in hamster liver |
title_full | Divergent effects of glutathione depletion on isocitrate dehydrogenase 1 and the pentose phosphate pathway in hamster liver |
title_fullStr | Divergent effects of glutathione depletion on isocitrate dehydrogenase 1 and the pentose phosphate pathway in hamster liver |
title_full_unstemmed | Divergent effects of glutathione depletion on isocitrate dehydrogenase 1 and the pentose phosphate pathway in hamster liver |
title_short | Divergent effects of glutathione depletion on isocitrate dehydrogenase 1 and the pentose phosphate pathway in hamster liver |
title_sort | divergent effects of glutathione depletion on isocitrate dehydrogenase 1 and the pentose phosphate pathway in hamster liver |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435027/ https://www.ncbi.nlm.nih.gov/pubmed/32812387 http://dx.doi.org/10.14814/phy2.14554 |
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